The efficacy of zidovudine (ZDV) for the prevention of mother-to-child transmission of HIV established by ACTG 076 has been confirmed in all subsequent studies in all settings. Despite the use of ZDV prophylaxis and breastfeeding, significant HIV transmission still occurs in utero and during delivery. Planned c-section in women receiving ZDV has been shown to nearly eliminate intrapartum transmission, but its use may be associated with increased morbidity and cost, especially in developing countries. The use of additional antiretrovirals during labor and delivery could be an alternative, and nevirapine (NVP), a potent antiretroviral, may be the drug of choice. When a single NVP dose was given to the mother during labor and to the infants 3 days after birth, the risk of intrapartum and early postnatal infection was dramatically reduce in a recent African study where women breastfed their infants. The primary objective of the proposed study is to assess the efficacy, safety and tolerance of a single dose of NVP given to women at onset of labor and to their infant 48 to 72 hours after birth, in addition to the current Thai ZDV prophylaxis regiment. Secondary objectives are to study the respective roles of the maternal and the infant NVP, further explore the physiopathology and timing of vertical HIV transmission and study co-factors of transmission (clinical status, term mode of delivery; viral load, phenotype and coreceptor use; host genetics and cellular immune response; and NVP and ZDV resistance-related mutations). To meet these objectives, we propose a phase III, double-blind, randomized, placebo controlled trial of 200mg NVP given to women at onset of labor and 2mg/kg to the infant 48 to 72 hours after birth, in addition to the current Thai ZDV regimen (ZDV starting at 34 weeks of gestational age, continuing through labor and delivery, and 1 week of infant ZDV). The study population will be consenting HIV-1 infected pregnant women enrolled in the Tahi MOPH ZDV prevention program and their non-breastfed newborns, 1,530 women will be randomized in one of 3 study arms: NVP/mother-NVP/infant or Placebo/mother-Placebo/infant arms for the primary comparison; or NVP/mother-Placebo/infant, an intermediate arm that will provide additional information as to the relative importance of the treatment of the mother and the treatment of the infant in the transmission of HIV-1. The primary endpoint is infant HIV status based on confirmed DNA-PCR results on specimens drawn at birth, 6 weeks, 4 months and 6 months. The study will build on the Perinatal HIV Prevention Trial (PHPT) in Thailand, a collaborative effort between Harvard University, IRD-France, the Ministry of Public Health of Kingdom of Thailand, and Mahidol and Chiang Mai Universities, using the study team, resources and network of clinicians already established in 27 hospitals throughout Thailand (mainly in Bangkok and the eastern and northern provinces of Thailand).